3D printed organs on a chip could one day put an end to animal testing

Oct 24, 2016 | By Nick

The heart-on-a-chip is entirely 3D printed with built-in sensors that measure the contractile strength of the tissue, providing scientists with new possibilities for studying the musculature of the heart. CREDIT: Johan Lind, Disease Biophysics Group/Lori K. Sanders, Lewis Lab/Harvard University

Researchers from the Wyss Institute for Biologically Inspired Engineering at Harvard University and the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS) have 3d printed ‘organs on a chip’ with fully integrated sensing that could mean an end to animal testing and change medical research.

Organs-on-chips can have a good deal of the native structure and function of a specific organ. So far the researchers have managed to create viable tissue microarchitecture for the heart, lungs, tongue and intestine.

Inevitably this isn’t a complete organ, but it gives a cross section of the tissue and researchers can then carry out a range of experiments and gain instant feedback from the onboard sensors that can measure the contractile strength and other responses to drug treatments and even induced diseases and conditions.

This system can also provide researchers with a wider cross-section of ‘patients’ for more efficient clinical studies and they can create complex situations, conditions and circumstances to test a drug or compound. It also means they can have a huge number of test subjects with none of the problems that you get with animal testing or human subjects.

Aside from the ethical concerns with animal testing, it is also extremely inefficient as the researchers have to study the effects of a compound on each animal with multiple blood tests and even surgical procedures. Even housing the animals can add significantly to the costs and restrict the number of test subjects in a study.

If we can distill the whole process down to simple tissue on a chip in a reliable and repeatable format, then, then this could be a huge boost for the medical research community.

"This new programmable approach to building organs-on-chips not only allows us to easily change and customize the design of the system by integrating sensing but also drastically simplifies data acquisition," said Johan Ulrik Lind, a postdoctoral fellow at the Harvard John A. Paulson School of Engineering and Applied Sciences (SEAS).

Cardiac tissue self assembles on the chip, guided into place by the 3D printed microstructures. Credit: Francesco S. Pasqualini and Johan U. Lind/Disease Biophysics Group

With animal testing, it can be nigh-on impossible to study gradual changes and it turns a lot of tests into simple black and white results when subtle shades of grey could help to produce better drugs and treatments.

The chip has a number of different wells that separate out the individual tissues and sensors, which means that the researchers can study a variety of tissues and treatments simultaneously. The researchers demonstrated the importance of this feature by producing a long-term drug study that showed the gradual changes in contractile stress in a fabricated cardiac tissue. This can change over the course of several weeks and is simply impossible to study effectively in live subjects.

"Researchers are often left working in the dark when it comes to gradual changes that occur during cardiac tissue development and maturation because there has been a lack of easy, non-invasive ways to measure the tissue functional performance," said Lind. "These integrated sensors allow researchers to continuously collect data while tissues mature and improve their contractility. Similarly, they will enable studies of gradual effects of chronic exposure to toxins."

"Translating microphysiological devices into truly valuable platforms for studying human health and disease requires that we address both data acquisition and manufacturing of our devices," said Parker. "This work offers new potential solutions to both of these central challenges."

In the future, these microphysiological systems could be tailored to mimic the effects of a specific disease or we could even have custom organs that match up to a specific patient’s physiology. It’s high-brow science, but with a complete match then doctors could test a series of drug combinations or run a computer model that gives them the best possibly treatment options.

"Our microfabrication approach opens new avenues for in vitro tissue engineering, toxicology and drug screening research," said Kit Parker, Tarr Family Professor of Bioengineering and Applied Physics at SEAS.

The heart-on-a-chip is made entirely using multi-material 3D printing in a single automated procedure, integrating six custom printing inks at micrometer resolution. CREDIT: Johan Lind, Disease Biophysics Group/Lori K. Sanders (Lewis Lab)/Harvard University

Inevitably it’s a complex and expensive process to create the chips, with are produced using a multi-material lithographic 3D printing process. Harvard University’s team developed a new production process and a series of different 3D printable inks that have helped them ramp up the complexity of the organs on a chip.

Now they have six inks with integrated soft strain sensors that build in to the tissue structure itself. That means they can produce a microphysiological representation of the human heart, complete with sensors, in one print.

"We are pushing the boundaries of three-dimensional printing by developing and integrating multiple functional materials within printed devices," said Jennifer Lewis, Hansjorg Wyss Professor of Biologically Inspired Engineering. "This study is a powerful demonstration of how our platform can be used to create fully functional, instrumented chips for drug screening and disease modeling."

3D printing is becoming an integral part of modern medical research and producing the essence of an organ on a chip could prove invaluable and help the medical community take on diseases and conditions that cause millions of deaths each and every year.

We are on the cusp of a new dawn in medical science and organs on a chip is just the start.